Antimony compounds have an extensive history of medical usage as anthelmintic agents. Trivalent antimonial compounds such as tartar emetic (potassium antimony tartrate), and sodium antimony-meso-2,3-dimercaptosuccinate remain the most widely used treatment for schistosomiasis. Schistosoma japonium is especially resistant to all treatment other than antimony compounds. These antimonial agents are quite effective but have toxic side effects which require that the patient be monitored closely during administration of the drug. The toxicity of these compounds may be attributed in a large part to the release of unchelated antimony and its subsequent interaction with binding sites in blood and tissues, particularly sulfhydryl sites in enzymes. We propose to examine the solution behavior of known antimony anthelmintics in order to establish the relationship between the nature of the binding of antimony and the toxicity vs. chemotherapeutic effectiveness of the drug. The properties of the antimonials which will be investigated are (1) their solution structures (the nature of binding of antimony), (2) their stability constants (the strength with which antimony is bound), (3) their tendency toward hydrolysis (resulting in the release of antimony), (4) their tendency to form "mixed chelates" with additional ligands and (5) the tendency of the ligand to stabilize the oxidation state of antimony. We will employ nuclear magnetic resonance (H1 and C13) spectroscopy, potentiometric titrations, absorption, spectroscopy and cyclic voltammetry to study the antimonial compounds. These studies, viewed in the light of other factors which determine drug efficacy, such as absorption by helmintics, excretion by host, will point the way toward the improved design of less toxic antimonial anthelmintics. In addition to the studies involving existing antimonials, a wide variety of new antimonial compounds will be synthesized, characterized by the above techniques and evaluated for schistosomicide activity.